Water → HCID 178491497, compound

HRID 1754065Notes

Reaction equation

HRID 1754065 reaction equation
[CH:1]1([NH:6][C:7]2[N:11]3[N:12]=[CH:13][C:14]([C:15]#[N:16])=[C:10]3[NH:9][C:8]=2[C:17]2[CH:22]=[CH:21][C:20]([O:23][CH3:24])=[CH:19][C:18]=2[O:25][CH3:26])[CH2:5][CH2:4][CH2:3][CH2:2]1.[OH2:27]>CS(C)=O>[NH2:9][C:10]1[N:11](/[C:7](=[N:6]/[CH:1]2[CH2:5][CH2:4][CH2:3][CH2:2]2)/[C:8]([C:17]2[CH:22]=[CH:21][C:20]([O:23][CH3:24])=[CH:19][C:18]=2[O:25][CH3:26])=[O:27])[N:12]=[CH:13][C:14]=1[C:15]#[N:16]

Participants

4

Reactant 2

HCID 962WaterHCID 178489026HCID 178489026, compound

Product 1

HCID 178491497HCID 178491497, compoundYield 19.7%

Reagents, catalysts & solvents 1

HCID 679Dimethyl SulfoxideSolvent

Procedure

A light brown solution of 3-(cyclopentylamino)-2-(2,4-dimethoxyphenyl)-1H-imidazo[1,2-b]pyrazole-7-carbonitrile (1.09 g, 3.1 mmol) in DMSO (200 mL) was stored for 35 days at RT. Within 24 h, it became a dark brown solution. After 35 days, LC/MS analysis indicated the absence of starting material and the presence of a strong desired peak. Then, it was poured into water (1 L) and the resulting cloudy brown solution was extracted with ethyl acetate (2×200 mL). Then, the combined extracts were washed with water and brine solution (2 L) to remove the DMSO. The organic layer was dried over anhydrous MgSO4, filtered, and concentrated to give the red brown paste (1.25 g) which was purified using an ISCO (150 g) column chromatography eluting with 0-40% ethyl acetate in hexanes. The desired fractions were combined and the solvent was removed under vacuum to obtain 224 mg (19.7% yield) of (E)-5-amino-1-(1-(cyclopentylimino)-2-(2,4-dimethoxyphenyl)-2-oxoethyl)-1H-pyrazole-4-carbonitrile as an off-white solid. 1H NMR (400 MHz, DMSO-d6) δ: 1.40-1.85 (br m, 8H), 3.66 (m, 1H), 3.66 (s, 3H), 3.87 (s, 3H), 6.62 (d, J=2.4 Hz, 1H), 6.71 (dd, J=2.4 and 9.0 Hz, 1H), 7.63 (s, 1H), 7.86 (d, J=9.0 Hz, 1H), 8.05 (brs, 2H). LC/MS calcd. for C19H21N5O3 (m/e) 367.4, obsd. 368.0 (M+H, ES+).

Workup

  1. waitAfter 35 days
  2. extractionthe resulting cloudy brown solution was extracted with ethyl acetate (2×200 mL)
  3. washThen, the combined extracts were washed with water and brine solution (2 L)
  4. customto remove the DMSO
  5. dry with materialThe organic layer was dried over anhydrous MgSO4
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customto give the red brown paste (1.25 g) which
  9. customwas purified
  10. washeluting with 0-40% ethyl acetate in hexanes
  11. customthe solvent was removed under vacuum

Sources & evidence

ORD record
ord-352d4b9658a243a790773b8169d883cd
Source dataset
uspto-grants-2015_10
Patent number
US09169215B2

Reaction notes

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